Since mothers frequently become immunized to paternal antigens carried by the fetus, developing offspring are potentially at risk with respect to defects caused by maternal IgG antibodies that pass the fetal-maternal barrier. We use the mouse as a model system in which genetic and environmental variables can be manipulated relatively easily to characterize such defects, particularly the maternally-influenced gammopathies that are generated in infancy but suppress IgG antibody production in adolescent and adult animals. Furthermore, we approach the problem by analyzing the normal development and function of the lymphocytes (B cells and T cells) that produce or regulate antibody production and then determining the effects of perinatal antibody treatments on these cell populations and functional mechanisms. We plan to use the Fluorescence Activated Cell Sorter (FACS) and monoclonal antibodies to define and characterize the functions of B cell and T cell subpopulations in normal, immunodefective and antibody-treated mice. In addition, we will use DNA transformation and other molecular biology methods to clone (some of) the genes coding for B cell and T cell subpopulation markers and will then examine the evolutionary genetics and molecular regulatory mechanisms controlling the expression of these genes. At the whole animal level, we hope to develop a "map" of regulatory interactions that will facilitate prediction of response characteristics under various kinds of stress. Thus, we will compare the suppressive effects of treatments with monoclonal antibodies to different cell surface determinants. We will then contrast these effects with the kinds of suppression induced by sequential immunization protocols that we have established and attempt to define the relationship between antibody-induced B cell deficits and antigen-dependent suppression induction.